Arthritis, an inflammatory disease of the joint, occurs in various forms such as rheumatoid arthritis and in related diseases with joint inflammation.
Rheumatoid arthritis, also called chronic rheumatoid arthritis, in particular, is a chronic multiple arthritis characterized by inflammatory changes in the synovial membrane of the particular capsule inner layer. Arthritis like rheumatoid arthritis are progressive and cause joint disorders such as deformation and acampsia, often resulting in severe physical disorders due to a lack of effective treatment and subsequent deterioration.
Traditionally, these forms of arthritis have been chemotherapeutically treated with various agents, including steroids and other adrenocortical hormones (e.g., cortisone), non-steroidal anti-inflammatory agents (e.g., aspirin, piroxicam, indomethacin), gold agents (e.g., auro-thiomalate), antirheumaticagents (e.g., chloroquine preparations, D-penicillamine), anti-gout agents (e.g., colchicine), and immunosuppressors (e.g., cyclophosphamide, azathioprine, methotrexate, levamisole).
Japanese laid-open Publication No. 10-36374 (1998) or PCT International Application Laid-Open No. WO97/40050 show thienopyridine derivatives or thienodipyridine, derivatives as an anti-inflammatory agent, especially as a therapeutic agent for arthritis.
However, steroids such as adrenocortical hormones and non-steroidal anti-inflammatory agents have drawbacks such as severe adverse reactions and adverse reactions hampering the drug's long-term use.
Although thienopyridine derivatives and thienodipyridine derivatives concretely disclosed in Japanese laid-open Publication No. 10-36374 (1998) or PCT International Application Laid-Open No. WO97/40050 have an anti-inflammatory activity, and especially therapeutical effect for arthritis, they tend to be affected by the metabolism of the body, so that, ratio of non-metabolized form of these derivatives in a body also tends to be lower.
Accordingly, there is a need for the development of a drug which is stable to metabolism by the body and exhibits excellent anti-inflammatory activity, bone resorption inhibitory activity and activity in inhibiting production of immunocytokines.